Relationship between inflammation and oxidative stress and its effect on multiple sclerosis.

INTRODUCTION: This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease. DEVELOPMENT: The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage. CONCLUSION: Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.

A comparative study of melatonin and immunomodulatory therapy with interferon beta and glatiramer acetate in a mouse model of multiple sclerosis. / Estudio comparativo de melatonina contra los tratamientos inmunomoduladores (interferón beta y acetato de glatirámero) en un modelo murino de esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a chronic, demyelinating, autoimmune disease of the central nervous system causing neuroinflammation. Experimental autoimmune encephalitis (EAE) is a model of the disease. MS is classically treated with interferon beta (IFN-ß) and glatiramer acetate (GA). Melatonin (MLT) has been reported to modulate immune system responses. The aim of the present study is to analyse the effects of MLT administration in comparison with the first-line treatments for MS (IFN-ß and GA). METHODS: EAE was induced in male Sprague-Dawley rats; the animals subsequently received either IFN-ß, GA, or MLT. Cerebrospinal fluid (CSF) samples were analysed by multiplex assay to determine the levels of proinflammatory cytokines. The neurological evaluation of EAE was also recorded. RESULTS: All immunised animals developed EAE. We evaluated the first relapse-remission cycle, observing that IFN-ß and GA had better results than MLT in the clinical evaluation. Neither EAE nor any of the treatments administered modified CSF IL-1ß and IL-12p70 concentrations. However, IFN-ß and MLT did decrease CSF TNF-α concentrations. CONCLUSIONS: Further studies are needed to evaluate the molecular mechanisms involved in the behaviour of MLT in EAE, and to quantify other cytokines in different biological media in order for MLT to be considered an anti-inflammatory agent capable of regulating MS.

Human papillomavirus viral load in cervical intraepithelial neoplasia as a prognostic factor in a Mexican population.

Persistent infection with human papillomavirus (HPV) has been recognized as the main etiological factor of morbimortality in cervical cancer. Several factors have been associated with the development of cervical disease, but viral load has recently been proposed as an indicator of cervical neoplasia. Therefore, a single measurement of viral load could be a suitable biomarker. We examined HPV viral load as a prognostic biomarker of cervical neoplasia. We used cervical scrapes to determine the total HPV viral load of 46 Mexican patients with various stages of cervical intraepithelial neoplasia (CIN) using hybrid capture assay coupled with a quantitative polymerase chain reaction method for cellularity estimation. Viral load values of CIN2 and CIN3 samples were compared with samples without cervical pathology (WP); all values of viral load were normalized by number of cells analyzed. The analysis showed significant differences in viral load between CIN2 and WP samples (P = 0.01) and between CIN3 and WP samples (P = 0.02). By contrast, no significant difference was detected between viral loads in CIN2 and CIN3 samples. The results showed significant difference between viral loads in CIN2 and CIN3 samples and that in WP samples. HPV viral load was significantly different between patients with CIN2-CIN3 and those with WP and can be used as a predictor of lesions.

Low frequency of human papillomavirus DNA in breast cancer tissue.

Human papillomavirus (HPV) is considered the aetiological agent for cervical cancer. Several reports have addressed a relationship with HPV and breast cancer, as different HPVs have been identified. The purpose of this study was to detect HPV DNA in 67 breast cancer patients and 40 non-malignant disease breast tissues by means of Polymerase Chain Reaction with consensus primers. The frequency of HPV in the cases group were 4.4% (3/67) and no positive samples among the reference group were identified. From the 3 positive samples, HPV types 16, 18 and 33 were identified by restriction patterns and direct sequencing. The high diversity among detection in the related studies shows that population genomic heterogeneity plays an important role in the disease. The low frequency detected in the present study suggests that HPV does not play an important role in breast cancer.

[Frequency of the IVS4+66A-G polymorphism in the alpha-synuclein gene in patients with Parkinson's disease in north-western Mexico]. / Frecuencia del polimorfismo IVS4+66A-G en el gen alfa-sinucleína en pacientes con enfermedad de Parkinson del noroccidente de México.

INTRODUCTION: Parkinson disease (PD) is the second most common neurodegenerative disease of adult onset. Is a progressive movement disorder including tremor, bradykinesia, rigidity and postural instability, with an age onset between 43 and 66 years. Histopathologically, is characterized by a severe loss of dopaminergic neurons in the substantia nigra and inclusions consisting of insoluble protein aggregates called Lewy bodies, this are comprised in part of alpha-synuclein. The etiology of PD is still not fully understood, but genetic analyses, epidemiologic studies and experimental models of PD are providing important new insights into the pathogenesis of PD. AIM: To determine allelic and genotypic frequencies of polymorphism IVS4+66A-G in the alpha-synuclein gene and to demonstrate its association with PD in northwest Mexican population. SUBJECTS AND METHODS: Genomic desoxyribonucleic acid (DNA) from 51 PD patients and 121 persons without PD were achieved by polymerase chain reaction and analyzed the allelic and genotypic distribution in IVS4+66A-G polymorphism of alpha-synuclein gene. RESULTS: The genotypic frequency of IVS4+66AA was 43.1% in PD patients and 38.8% in control group; IVS4+66GG was 2% in PD patients and 4.1% in control group, whereas 54.9% in PD patients and 57.1% in control group were heterozygous. Statistical differences were not observed between groups (p<0.05). CONCLUSIONS: Association was not observed between the IVS4+66A-G polymorphism and PD.

Cytochrome P4501A1 polymorphism is associated with susceptibility to acute lymphoblastic leukemia in adult Mexican patients.

We studied the role of cytochrome P4501A1 (CYP1A1 Val/Val) genotypes in the etiology of acute lymphoblastic leukemia (ALL) in adult Mexican patients. Distributions of CYP1A1 Val/Val genotypes in peripheral blood DNA samples from 136 healthy controls and 136 adult patients with ALL were evaluated. There was an increased frequency of the CYP1A1 Val/Val genotype among ALL patients, showing a significant association between this genotype and the risk of developing ALL.